ATP cone

{{Infobox protein family

| Symbol = ATP-cone

| Name = ATP-cone

| image = PDB 7r1r EBI.jpg

| width =

| caption = ribonucleotide reductase e441q mutant r1 protein from escherichia coli

| Pfam = PF03477

| Pfam_clan =

| InterPro = IPR005144

| SMART =

| PROSITE =

| MEROPS =

| SCOP = 7r1r

| TCDB =

| OPM family =

| OPM protein =

| CAZy =

| CDD =

}}

In molecular biology, the ATP-cone is an evolutionarily mobile, ATP-binding regulatory domain which is found in a variety of proteins including ribonucleotide reductases, phosphoglycerate kinases and transcriptional regulators.{{cite journal |vauthors=Aravind L, Wolf YI, Koonin EV | title = The ATP-cone: an evolutionarily mobile, ATP-binding regulatory domain | journal = J. Mol. Microbiol. Biotechnol. | volume = 2 | issue = 2 | pages = 191–4 |date=April 2000 | pmid = 10939243 }}

In ribonucleotide reductase protein R1 from Escherichia coli this domain is located at the N terminus, and is composed mostly of helices.{{cite journal |vauthors=Uhlin U, Eklund H | title = Structure of ribonucleotide reductase protein R1 | journal = Nature | volume = 370 | issue = 6490 | pages = 533–9 |date=August 1994 | pmid = 8052308 | doi = 10.1038/370533a0 | s2cid = 8940689 }} It forms part of the allosteric effector region and contains the general allosteric activity site in a cleft located at the tip of the N-terminal region.{{cite journal |vauthors=Eriksson M, Uhlin U, Ramaswamy S, Ekberg M, Regnstrom K, Sjoberg BM, Eklund H | title = Binding of allosteric effectors to ribonucleotide reductase protein R1: reduction of active-site cysteines promotes substrate binding | journal = Structure | volume = 5 | issue = 8 | pages = 1077–92 |date=August 1997 | pmid = 9309223 | doi = 10.1016/S0969-2126(97)00259-1| doi-access = free }} This site binds either ATP (activating) or dATP (inhibitory), with the base bound in a hydrophobic pocket and the phosphates bound to basic residues. Substrate binding to this site is thought to affect enzyme activity by altering the relative positions of the two subunits of ribonucleotide reductase.

The ATP-cone domain also is a key part of NrdR, that controls transcription of ribonucleotide reductases in bacteria, in response to ATP and dATP levels. {{Cite journal |last=Rozman Grinberg |first=Inna |last2=Martínez-Carranza |first2=Markel |last3=Bimai |first3=Ornella |last4=Nouaïria |first4=Ghada |last5=Shahid |first5=Saher |last6=Lundin |first6=Daniel |last7=Logan |first7=Derek T. |last8=Sjöberg |first8=Britt-Marie |last9=Stenmark |first9=Pål |date=2022-05-16 |title=A nucleotide-sensing oligomerization mechanism that controls NrdR-dependent transcription of ribonucleotide reductases |url=https://www.nature.com/articles/s41467-022-30328-1 |journal=Nature Communications |language=en |volume=13 |issue=1 |doi=10.1038/s41467-022-30328-1 |issn=2041-1723 |pmc=9110341 |pmid=35577776}}